KEY TAKEAWAYS
- The LOTIS-5 phase III trial aimed to evaluate the safety and effectiveness of Lonca-R as a treatment for R/R DLBCL patients.
- The primary outcome measure was PFS.
- The result demonstrated that Lonca-R combo safely shrinks lymphoma tumors in early tests, offering a potentially shorter treatment option. Further studies are ongoing.
Loncastuximab tesirine (Lonca) is an antibody-drug conjugate designed for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) following at least two systemic treatments. This consists of an anti-CD19 monoclonal antibody linked to a pyrrolobenzodiazepine dimer toxin. Researchers aimed to evaluate the safety and effectiveness of Lonca+rituximab (Lonca-R) as a treatment for R/R DLBCL patients.
The study, with a primary outcome of progression-free survival(PFS), initially enrolled 20 patients in a nonrandomized safety run-in (part 1). Updated results from new safety and efficacy data were presented at SOHO 2022.
Part 2 of the study planned to randomize approximately 330 patients into Lonca-R or rituximab-gemcitabine-oxaliplatin arms. Key inclusion criteria included age ≥18, DLBCL(including transformed from indolent lymphoma) or high-grade B-cell lymphoma with specific genetic rearrangements, at least one prior therapy line, ineligibility for stem cell transplantation, and measurable disease according to the 2014 Lugano classification.
The intervention involved receiving 0.15 mg/kg Lonca plus 375 mg/m2 rituximab every 3 weeks for 2 cycles, followed by 0.075 mg/kg Lonca plus 375 mg/m2 rituximab every 3 weeks for up to 6 additional cycles.
In Part 1, patients with a median age of 74.5 years received a median of 5 cycles of Lonca-R and had one prior therapy. About 7 patients completed treatment, and 5 are still in follow-up.
As of April 10, 2023, 11 (55%) patients experienced grade ≥3 treatment-emergent adverse events (TEAEs). The most common grade ≥3 TEAEs were increased gamma-glutamyl transferase (5 patients [25%]) and neutropenia (3 patients [15%]).
The central review reported an overall response rate(ORR) of (80%)16/20 patients; (50%) achieved complete response(CR), and (30%) achieved partial response. The median duration of response was 8.0 months (95% CI: 3.2, –), and the median PFS was 8.3 months (95% CI: 4.5, –).
The result demonstrated that Lonca-R combo safely shrinks lymphoma tumors in early tests, offering a potentially shorter treatment option. Further studies are ongoing.
Source: https://clml-soho2023.elsevierdigitaledition.com/440/index.html
Clinical Trial: https://clinicaltrials.gov/study/NCT04384484
Kwiatek M, Grosicki S, López Jiménez J, Felipe Pinzón Mariño S, Snauwaert S, Kingsley E, Zacchetti G, Wang Y, Wang L, Depaus J, et al. Updated Results of the Safety Run-In of the Phase 3 LOTIS-5 Trial: Novel Combination of Loncastuximab Tesirine With Rituximab (Lonca-R) Versus Immunochemotherapy in Patients With R/R DLBCL.
